The goal of this project is to characterize the function of B lymphocyte FcGamma receptors. Previous findings indicate that the FcGamma receptors of B lymphocytes interact with: a) the lymphocyte cytoskeleton, b) Ia antigens, c) LyM antigens, d) surface IgM, and e) surface IgD. Each of these interactions is distinct, specific, and non-random. Studies utilizing antigen-antibody complexes and monoclonal anti-FcGamma receptor antibodies indicate that B lymphocyte FcGamma receptors cross-linked by their physiologic ligand down-regulate B lymphocyte differentiation without affecting proliferation. Resting but not activated B lymphocytes are susceptible to this negative regulation. Occupancy of B lymphocyte surface IgM by a separate ligand is necessary for inhibition to occur, suggesting that the previously described interaction between these two membrane receptors may be involved in generating the negative signal. Monoclonal anti-FcGamma receptor antibodies on a Sepharose matrix but not in soluble form affect B lymphocyte function in a fashion similar to antigen antibody complexes. This result suggests that certain monoclonal antibodies specific for cell surface receptors must be presented in a form which will produce effective cross-linking in order to obtain functional effects. Various B lymphocyte populations have been evaluated for susceptibility to FcGamma receptor mediated downregulation. LyB5 negative B cells are susceptible but antigen-primed B cells are not. B cells from autoimmune MRL/1 mice are susceptible but not those from autoimmune NZB mice. Lack of responsiveness to FcGamma receptor downregulation may play a pathogenic role in NZB autoimmune mice.